Chapter 91. Care of the Multiorgan Donor

• Increasingly successful solid organ transplantation has increased the need for organ donors.
• Maximizing organ procurement and expanding donor acceptance criteria should decrease the organ shortage.
• Aggressive ongoing critical care of the multiorgan donor is essential to improve organ retrieval and posttransplant graft performance.
• Understanding the process of brain death is essential for directing donor treatment strategies to ensure preservation and function of donor organs.
• The goals of management of the multiorgan donor are to maximize organ function by maintaining organ perfusion and oxygenation, and to promptly recognize and treat potential complications such as hypotension, dysrhythmia, pulmonary edema, massive diuresis, coagulopathy, hypothermia, and sepsis.

Organ transplantation has evolved rapidly from the first early successes to the current widespread use of donated organs for the treatment of end-stage kidney, liver, heart, and lung failure.1 The success of solid organ transplantation has increased the need for an expanded supply of organ donors. In response to this need, the age limit for cadaveric donors has been increased, and donors over the age of 50 years are now routinely used. The use of organs from living related donors, living unrelated donors, and non–heart-beating donors (those declared dead on the basis of cardiopulmonary criteria) has also increased. Nevertheless, there has been a progressively widening gap between the number of patients waiting for transplants and the number of transplantations performed. The number of patients on the national waiting list was 25% higher than the number of transplantations in 1988.2 According to the United Network for Organ Sharing (UNOS), as of April 24, 2003, the number of patient registrations was 81,208, with the majority of patients in the 18- to 64-year age range. In 2002 a total of 24,847 transplants were performed, thus the number of patients on the waiting list was about 325% higher than the number of transplanted patients.3

In the past 10 years, the waiting list has increased 229%, and waiting list deaths have increased 192%. In contrast, during this same time period, the number of cadaveric organ donors has increased only 32%, with donors younger than 50 years of age increasing only 10.3%. The largest increase in cadaveric donors has been in donors older than 50 years of age (135%). One consequence of the increased proportion of older and more diverse donors has been the increase in organs discarded after they had been procured.3

The relevance of a properly functioning transplanted organ cannot be overemphasized and is clearly crucial for the success of transplantation of organs requiring immediate function such as the heart and lung. Temporary failure of the liver, kidneys, and pancreas may be tolerated with supportive measures such as hemodialysis and pharmacologic interventions. Early graft failure accounts for approximately 30% of all deaths of cardiac and lung recipients, and the deaths of 30% of liver and 5% of renal recipients.4

At a time when transplant surgeons are facing an increasing number of deaths on the waiting list, and as the size of the list continues to grow, there has never been a greater need to utilize a higher percentage of older or otherwise marginal donors, minimize the incidence of primary graft nonfunction, and develop organ donor management strategies that continue to increase the number of organs available for transplant.3,4–6

To increase the number of transplantable organs, UNOS created the Critical Pathway for the Organ Donor, a blueprint of an organ donor's treatment plan. The Critical Pathway is a concise, one-page document designed to help critical care staff and procurement coordinators understand and follow the steps required for effective donor management.3

After brain death has been declared in potential organ donors and consent is given for donation, donors need to be medically managed to keep their organs viable until organ recovery can occur. The Critical Pathway describes optimal care for the organ donor and maps the process to improve the outcome for successful organ transplantation. The Pathway promotes collaboration between organ procurement coordinators and critical care staff, and delineates roles to prevent duplication of effort or confusion.

Recent studies have shown that the Critical Pathway, which has been endorsed by four major transplantation associations, significantly increased the number of organs procured and transplanted from brain-dead donors.3,5,6 There is no sacrifice in the quality of the transplanted organs or an increase in donor management time.

The two most limiting factors in organ donation today are: (1) failure to identify patients that are potential organ donors and lack of referral of those patients to the organ procurement organization, and (2) refusal of patients' families to consent to donation. A proactive donor detection program maintained by well-trained transplant coordinators, the introduction of systematic death audits in hospitals combined with a positive social atmosphere, appropriate management of mass media relations, and appropriate economic reimbursement for the hospitals are the measures advocated by the Spanish model, which has resulted in the highest continuous increase by far in cadaveric organ donation within a large country, reaching 32.5 organ donors per million population in 2001.7

Once a patient has been identified as a potential organ donor, the critical pathway should be initiated by contacting the local organ procurement organization to make the referral. Referral is critical; if this does not occur the opportunity for donation may be lost entirely. Organ procurement organization staff may wish to be notified as the condition of the patient deteriorates even before brain death occurs. Most often, the organ procurement organization can quickly do a preliminary assessment to determine whether the patient is a potential candidate for organ donation. If the patient is not a candidate, there is no need to discuss the option of donation with the patient's family members, and the pathway is stopped. Furthermore, if family members broach the subject of organ donation, a clear answer can be provided as to why the patient is not a candidate for donation, and any confusion can be avoided. Even if a patient is not a candidate for organ donation, the family may have other options to consider, such as donations of eyes, skin, bone, and heart valves.8

Referral systems should be automatic and simple. Donors are lost when hospital staff with limited knowledge of the acceptance criteria for organ donors inappropriately rule out potential organ donors as medically unsuitable. Retrospective reviews of the records of patients who have died while in the hospital indicate that a surprising number of potential donors were never evaluated by organ procurement organization staff for this reason. The reasons given for the determination of unsuitability, if any reason is noted in the chart, are many, and include age, use of vasoactive drugs, disease (i.e., diabetes), cardiopulmonary resuscitation, and positive cultures. Any patient with a significant and potentially life-threatening injury to the head, whether caused by trauma, an intracerebral hemorrhage, or an anoxic event, should be referred to the organ procurement organization as early as possible for evaluation as a potential organ donor. This practice allows the organ procurement organization to evaluate the situation and apprise staff members early on about whether the patient is a potential donor or not. Currently, only a few medical contraindications to donation are absolute, including:

• Transmissible infectious disease that will adversely affect the recipient (i.e., human immunodeficiency virus (HIV) infection, active viral hepatitis B, encephalitis of unknown cause, prion disease, malaria, and disseminated tuberculosis)
• Active visceral or hematologic malignant neoplasm
• Characteristics that indicate the organ is unlikely to function

Indeed, the only typical feature of a potential donor today is brain death, and with the increased use of non–heart-beating donors in the United States, even brain death is not necessarily typical anymore.

Early referral is also key to success in recovering transplantable organs for potential recipients. If an organ procurement organization receives a referral from the critical care staff well after brain death has occurred, decreases in end-organ function will already have taken place. If the organ procurement organization is called in only well after the signs of brain death are present, the donor who might have had 5 to 7 organs suitable for donation and transplantation may by that time have only 1 or 2 suitable organs. It has been questioned whether it is reasonable to expect nurses and physicians to keep pace with all of the changes taking place in organ donation, and thus systems have been developed and implemented, sometimes required by law, that do not rely on hospital staff to screen potential donors.9

The introduction of successful kidney transplantation in the 1950s led to the concept of the use of organs from “heart-beating cadavers.” The clinical findings of “brain death” were first described by French investigators Mollaret and Gaulon in 1959, describing patients on ventilators who have loss of neurologic function after persistent deep coma and loss of spontaneous ventilation; they first called this condition “coma depassé” to denote neurologic damage beyond coma, but they did not equate this entity with death itself.10 In 1968, the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death was created to standardize the definition of brain death and resolve some of the growing controversies surrounding organ procurement for transplantation from heart-beating donors. The resolutions from this committee are known as the Harvard Criteria of Brain Death. The reasons for this redefinition of death, according to the aforementioned Committee, were the need to bring relief to the families of the sick, free up beds in the intensive care units, and remove the grounds for objecting to the obtaining of organs for transplantation.11

Two criteria were considered for determining brain death: either the irreversible loss of all of the functions of the entire brain, including the brain stem, or the irreversible loss of the functions of the brain stem only.

The concept of brain death continues to be a topic of international debate among medical clinicians, anthropologists, philosophers, and ethicists. Much of this discussion is the result of the awareness of continuing technological advances, neurodiagnostic developments, and clinical insight. This ongoing dialogue can be viewed as a dynamically developing process of achieving a multidisciplinary consensus that is responsive to a continually changing technological environment.11,12

It has been argued that brain death, either when referring to the entire brain or to the brain stem alone, is a concept without a precise clinical or pathologic basis, and for this reason, the criteria employed in its diagnosis are somewhat arbitrary. It has also been said that it is difficult or almost impossible to have diagnostic standards for a condition that has never been adequately defined.12

Evidence-based guidelines for determining the brain-death criteria in the United States are based on the Report of the Medical Consultants on the Diagnosis of Death to the President's Commission on the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research of 1981.

The President's Commission requires loss of brain stem function, loss of cortical function, and that the condition is irreversible. Although the guidelines reflect generic, scientifically based recommendations, adaptation of certain details may vary across practice settings and states according to variations in institutional policy and local legislation.11–13 The full description of the diagnosis of brain death is explained further in Chapter 67.

Refusal by the family to provide consent for donation is the most common reason that organs of medically suitable potential donors are not recovered. According to estimates, 35% of the medically suitable organ donors do not donate because the family of the potential donor refuses to consent to donation. Hospitals with low donation rates were more likely to have staff members who perceived dealing with a potential donor as time-consuming and burdensome, and who were uncomfortable with how their hospital handled donation. The role that personal attitudes play in the ability of staff members to handle donation is unclear. Staff members in hospitals with high donation rates have a more positive personal attitude toward donation than do staff members in hospitals with low donation rates; however, a positive personal attitude does not correlate with the ability to approach families about donation.9

Another situational variable that has a marked influence on donation rates is the timing of the request (i.e., when the request is made relative to when the family is informed of the death). Research clearly shows that inappropriate timing of the request (i.e., informing the family of the death and requesting donation at the same time) is a formula for family refusal. Families need time to acknowledge the death before they are approached about donation. Consent rates have been shown to increase from 18% to 60% if there was a delay between death and the request for donation. Ensuring that this delay occurs is referred to as “decoupling” of the request. The timing of the request has been evaluated in numerous studies, and all the researchers have reached the same conclusion: that decoupling the request leads to improved donation rates. However, despite vigorous attempts by the organ donation community to educate critical care staff, and by the health care community about the importance of decoupling the request, a significant number of requests are still “coupled.”9,14

Unfortunately, current medical school curricula generally lack training on how to break bad news and inform of death. It is important that the word “dead” should be pronounced and not avoided. At the brain death declaration, the main task of the intensive care unit staff is not that of obtaining consent for organ removal, but rather counseling and helping the family to cope with the grieving process. Minimizing the family's distress is the focus of care and is an essential prerequisite for a subsequent organ donation request.10

Unrestricted visits to the potential donor should not only be permitted, but actively encouraged. All the family's questions about brain death must be answered unhurriedly by the staff, and the right words should be used in front of a warm cadaver with a heart that is still beating. For example, it is better to use terms which strengthen the certainty of the death, such as “no, he does not breathe, but the ventilator forces the air into the lungs,” or “yes, the heart is still pumping the blood, and it will do so for some hours more because it is artificially stimulated and this is why the skin is warm.” No mention about organ donation should be raised before the concept of brain death is comprehended and the death is accepted by the family. The staff should refer to the dead patient using the past tense; as soon as family members begin to talk of him or her using “was,” the acceptance of death becomes clear. The physician who is in charge of the intensive care unit should only discuss brain death with the family. The discussion relating to organ donation should be introduced by the transplant coordinator so that there is a clear distinction between the two functions (i.e., treatment of the patient and preparation for donation). The request should be made by the transplant coordinator in a positive way. It should be proposed as an option that the hospital offers the family for helping other patients, rather than an apologetic or indifferent businesslike gesture. Those who have difficulty in requesting consent should delegate the task to more confident staff. The family must never be forced into making a hasty decision, and it is always advisable to let them take their time and discuss the matter among themselves and with other members of the family before asking again. Often an initial refusal turns into a convinced consent over the course of two or three meetings. While a firm refusal must be respected, hesitation can easily lead to authorization if the subject of the urgent need of organs for many patients, as a life-saving procedure or a dialysis-relieving therapy, is raised tactfully. The consent process for organ and tissue donation should not only be considered a necessity, but also a family's right.9

Obtaining consent for organ donation from families is enhanced by:

• Allowing time for families to accept death
• Having someone who is an expert in donation consent approach the family
• Approaching the family in a private, quiet area in an unhurried manner
• Involving nursing and the organ procurement organization staff in the coordination of the entire consent and donation process

Once consent for organ donation is given, a thorough evaluation is conducted. The organ procurement coordinator collaborates with the critical care nurse to obtain the necessary history and results of diagnostic tests. The donor's chart is reviewed for prehospital and emergency department entries for details of the events leading to admission. The duration of “downtime” (cardiopulmonary arrest) and cardiopulmonary resuscitation, vital signs, drugs administered, and obvious signs of chest and abdominal trauma are noted. If an old chart or the patient's primary physician is available, a pertinent medical history is obtained.

Completing a battery of laboratory tests in a timely manner will expedite organ placement and decrease the time required for donor management. A blood sample is also obtained from the donor, to perform bacteriologic and serological screening for infectious disease. This serological sample is usually sent to a central laboratory that performs such testingon a 24-hour basis; however, once the sample arrives at the laboratory, it usually takes about 6 hours for the results to be determined. Usually, the donation coordinator is aware of the serological results as the offers for organ-specific recovery are made.

The organ procurement coordinator reviews a comprehensive medical and social history with the appropriate family members or significant others. Donors are screened for a number of factors, including but not limited to, any history or treatment of heart disease, hypertension, chest pain, or diabetes; use of tobacco, drugs, and alcohol; and high-risk behaviors for transmission of human immunodeficiency and hepatitis viruses. Pertinent family history is reviewed also. The organ procurement coordinator does a complete physical examination of the donor, paying close attention to any finding that may influence organ integrity. The transplant surgeons determine the suitability of the donor with respect to the transplantable organs.8–10

Screening for Infectious Agents

Serological screening for HIV, human T lymphotropic virus (HTLV),hepatitis B virus (HBV), hepatitis C virus (HCV), and cytomegalovirus (CMV) is routinely performed along with screening for Treponema antigen (syphilis) and for Toxoplasma.

The presence of an active viral infection in the form of encephalitis or meningitis, varicella-zoster virus infection, or HIV infection is an absolute contraindication to organ donation because of the hazard that each of these clinical situations pose to the allograft recipient.

Isolated hepatitis B surface antibody positivity usually implies previous vaccination. Hepatitis B surface antigen (HBsAg) positivity reflects the presence of viral DNA in the blood that is related to current hepatitis B infection or a remote infection that has not cleared. These donors have contagious hepatitis B and will transmit the disease to the recipients unless the recipient has neutralizing antibodies due to previous exposure or vaccination. Patients who have acute hepatitis infection develop antibodies to the core antigen early in the course of the disease. Donors who are core antibody–positive should be considered infectious because they may be convalescing from acute infection. If both surface and core antibodies are positive, then the patient has recovered from hepatitis B and demonstrates immunity. Nevertheless, liver recipients from these donors are at significant risk for the development of acute hepatitis B infection, as opposed to the recipients of the other organs. Organs from these core-positive donors are generally reserved for patients with a documented response to the hepatitis B vaccine.15

All hepatitis C antibody-positive donors should be considered infectious. The hazard of HCV transmission from a previously infected organ donor is a concern for all allograft recipients. Approximately 5% of all organ donors are positive for antibody to HCV. The presence of antibody to HCV is indicative of HCV infection, because antibody to HCV appears in peripheral blood within 2 months of HCV exposure. Most organ procurement organizations have adopted a policy of screening organ donors for antibody to HCV. IgG antibody to HCV does not protect against donor organ contamination; however, it is also important to emphasize that detection of antibody to HCV by serological screening of the donor is not predictive of HCV transmission.

Although a positive screening result does not necessarily rule out organ donation, a selective strategy of reserving organs from HCV-positive donors for recipients with previous HCV exposure and detectable antibody to HCV can be applied. Transplantation of a liver from a donor positive for antibody to HCV to a recipient positive for antibody to HCV does not appear to cause increased morbidity or mortality. Transplantation of an HCV-positive heart or lung allograft when a HCV-negative recipient's life is in danger may be the only alternative to immediate death.16,17 Kidney recipients who are hepatitis C positive can shorten their time on the waiting list by accepting a kidney from a HCV-positive donor. Table 91-1 shows the relative risk of viral transmission for hepatitis B and C viruses.17

Transplantation of an organ from a CMV-positive donor can result in subsequent reactivation of latent virus and replication in the immunosuppressed host. The specific CMV serological status of the donor and recipient has implications for prophylaxis, the highest-risk group being CMV-seronegative recipients of CMV-seropositive donor organs (i.e., the so-called primary infection group).

Nevertheless, transplantation of organs from CMV seropositive donors has not been considered an absolute contraindication for transplantation, because the high seroprevalence of the virus among the general population makes it impractical to rule out such donors. Furthermore, recent evidence suggests that even mismatches between CMV-positive donors and CMV-negative recipients can be successfully overcome by strategies aimed at prophylaxis for CMV infection.

Over 95% of potential adult donors are seropositive (IgG antibody) for Epstein-Barr virus (EBV); thus serological screening of organ donors for EBV is not routinely performed. However, primary EBV infection (i.e., transplantation of an organ from an EBV-seropositive donor to an EBV-seronegative recipient) is associated with an increased risk of posttransplant lymphoproliferative disease. Therefore, recognition of this mismatch in a potential allograft recipient known to be EBV-negative may be important prognostic information. Currently, there is no effective means of preventing this complication.

The detection of antibody to treponemal antigen is not a contraindication to organ procurement, but it is a contraindication to tissue procurement. A standard course of penicillin therapy would provide sufficient antibiotic coverage to prevent syphilitic complications in an allograft recipient.

The possible transmission of the protozoan Toxoplasma gondii is a concern, especially for heart allograft recipients, because of the predilection of this parasite for muscle tissue. Organ procurement from seropositive donors is not contraindicated; however, the detection of seropositivity means that the recipient may be placed at high risk. Fortunately, the use of trimethoprim-sulfamethoxazole as prophylaxis for Pneumocystis carinii infection prevents transmission of T. gondii.16

Regional directives will need to be implemented as necessary with regard to novel infectious agents carrying alarming epidemic/pandemic life-threatening potential. Recently regions of North America have been faced with two relatively new entities, West Nile virus and the severe acute respiratory syndrome (SARS). Organ donors should be tested for evidence of both West Nile virus viremia by polymerase chain reaction (PCR) and early antibody response (IgM) to West Nile virus. If either test is positive the potential donor is to be deemed ineligible for organ donation.

SARS screening is currently conducted by using a specifically directed series of questions on the donor medical and social history questionnaire. This investigates the donor institution's category of contamination as determined by the infection control officer at that institution; the donor's clinical history relative to the last 10 days prior to donor assessment with regard to signs or symptoms associated with SARS; and epidemiologic links related to direct contact with SARS risk or travel to an area listed in the current Travel Health Advisory.18

Donor-Related Malignancies

Transmission of donor malignancies is rare, with 18 cases from 34,933 cadaver donors and 3 cases from 32,052 living donors being reported to UNOS from 1994 through 2001. Donors with past histories of certain types of cancers may be considered as donors, including certain types of primary central nervous system (CNS) tumors. Risks of cancer transmission from donors with a history of nonmelanoma skin cancer and selected cancers of the CNS appear to be small. When considering organ use from donors suffering from intracranial malignancies, there are a number of general guidelines. Most important is to consider the known biologic behavior of various CNS neoplasms and their propensity to spread outside of the cranial vault. Repeated craniotomies as well as ventriculoperitoneal or ventriculojugular shunts have been associated with increased risk of metastasis.17,19–21

Risks of tumor transmission with certain other types of cancer may be acceptable, particularly if the donor has a long cancer-free interval prior to organ procurement, while certain other cancers pose a high transmission risk. Tumors that pose a high transmission risk include choriocarcinoma, melanoma, lymphoma, and carcinoma of the lung, colon, breast, kidney, and thyroid.

A list has been developed outlining the relative risks of CNS tumor transmission from cadaver donor to allograft recipient (Table 91-2).

Cardiac Evaluation

An initial electrocardiogram (ECG) should be obtained on every potential cardiac donor, and additional ECGs should be obtained when changes in heart rhythm occur. ECG changes may be temporary and related to alterations in sympathetic output. Nonspecific ST-segment and T-wave changes, prolonged QT intervals, and T-wave inversion are common. Tachycardia is common and may be caused by diabetes insipidus, diuresis, hemorrhage, vasopressor therapy, or electrolyte disturbances. ECGs are evaluated for signs of acute myocardial injury.8

A transthoracic or transesophageal echocardiogram may be obtained to evaluate motion of the heart wall and valve function, estimate ejection fraction, and to detect a pericardial effusion. Transient changes that do not preclude heart donation include a stunned myocardium or myocardial depression related to acidosis and hypoxemia. If the causes of the changes are reversible, the heart may still be successfully transplanted. Although echocardiography is effective in screening for anatomic abnormalities of the heart, the use of a single echocardiogram to determine the physiologic suitability of a donor is not supported by clinical evidence. An alternative approach, using a pulmonary artery catheter to guide the physiologic assessment and management of ventricular dysfunction, has been used with success in the United Kingdom.

Assessment and management of donor left ventricular dysfunction offers the greatest potential to increase heart donor utilization. Strong evidence indicates that younger hearts with left ventricular dysfunction can recover normal function over time in the donor and after transplantation into a recipient. Metabolic abnormalities, anemia, and excessive doses of inotropes should be corrected prior to obtaining an echocardiogram. Aggressive donor management, including pulmonary artery catheterization and hormonal resuscitation, should be performed in donors with an initial left ventricular ejection fraction less than 45%. Table 91-3 shows the heart donor criteria recently modified to potentially expand the available pool of cardiac donors.17

Pulmonary Evaluation

The suitability of donor lungs for transplantation is determined with several diagnostic tests. A chest radiograph should be interpreted by a radiologist or qualified physician. A complete history of the donor's treatment while in the hospital, including the use of vasopressors and results of arterial blood gas analyses, are shared with centers considering the transplantation of lungs. Smoking history should be reported, along with the results of Gram stains of sputum (a specimen for detection of yeasts and fungi is desirable), and a description of the sputum characteristics. In addition, a bronchoscopic examination is performed to assess for signs of aspiration, and to document evidence of a foreign body or presence of blood or other material entering the lower airways from above. It also allows assessment of the character and amount of secretions in the lung and provides microbiologic specimens. A bronchoscopic examination will also promote pulmonary stability in the donor by removing airway secretions that may have accumulated. Blood gases are repeated every 3 hours to assess the results of interventions and to determine trends. Repeat pulmonary recruitment maneuvers are performed to optimize ventilation-perfusion matching.

Wider application of broader criteria for donor selection and procurement is possible and can clearly increase the size of the donor pool. If uniform multidisciplinary donor management protocols were developed, increased lung utilization would follow. Table 91-4 shows the current criteria that are used to determine the suitability of a cadaver lung donor. The Lung Transplant Working Group proposed the new criteria to include virtually any donor up to the age of 65 years, in the absence of significant lung injury from smoking, and absence of cancer with metastatic potential.8,17,22,23

In an effort to augment the donor pool, criteria have been loosened with the retrieval of organs from donors with greater smoking histories, infiltrates on radiography, or marginal gas exchange. Because these previously-considered marginal donors, or more appropriately termed “extended” donors, are now being used any potential brain-dead patient without obvious contraindication to cadaveric donation should be referred to appropriate local organ procurement agencies for final determination of suitability.17,23

Renal Evaluation

The discard rate of kidneys procured from cadaveric donors in the U.S. has been increasing to an alarming level of more than 15% of those kidneys recovered for transplantation. Approximately 50% of kidneys from cadaveric donors over 60 years of age (older-age donors) are not transplanted due to donor quality.

The renal system in a cadaveric donor undergoes a number of physiologic changes that are influenced dramatically by both the medical therapies used to prevent brain death and by brain death itself. The results of basic renal function tests such as measurement of serum levels of creatinine and urea nitrogen and urinalysis should be reviewed to provide a profile of renal system function in the donor since admission. When kidney donors are evaluated, the effect of hemoconcentration on the results of these studies should always be considered. Elevated levels of serum creatinine and urea nitrogen and atypical urinalysis findings may suggest that renal function was compromised. The relative risk of dialysis after transplantation is 1.5 times greater in recipients of kidneys from donors >55 years of age vs. those who are <55. Table 91-517 shows the latest approved expanded kidney donor criteria, based on the relative risk >1.7 of having a graft failure for donors older than 50 years of age with at least two of the following factors: creatinine >1.5 mg/dL, a cerebrovascular accident (CVA) as a cause of death, and hypertension, as compared to a reference group of nonhypertensive donors between the ages of 10 and 39 whose cause of death was not CVA, and whose creatinine was <1.5 mg/dL.1,8,17

Liver Evaluation

The assessment of a donor liver before transplantation has been the subject of much research; however, clinically one still relies on a subjective interpretation of donor data and the macro- and microscopic appearance of the liver to decide whether to use the graft. More reliable predictors of graft function are required. Significant efforts have been made to try to assess donor grafts by evaluating different aspects of liver function, including the ability of the liver to synthesize proteins, metabolize drugs, secrete bile, produce high-energy phosphates, and by following the levels of markers of microvascular injury. To date, many donor organs that were previously not considered suitable for transplantation, “marginal” grafts, are now being used in selected circumstances. The marginal donors are identified based on demographic, clinical, laboratory, and histologic data. This includes donor age >70 years or <3 months, donor body weight over 100 kg, moderate or severe macrovesicular fat infiltration of the liver, and abnormal liver function tests. Serum aspartate aminotransferase (AST) >160 IU/L, serum sodium >160 mmol/L, donor stay in intensive care of more than 5 days, significant periods of hypotension (<60 mm Hg systolic BP for more than 30 minutes associated with a rise in serum AST), and significant systemic infection are all parameters considered to define marginal grafts. Important in the assessment of potential grafts is the presence of hepatic steatosis: increased donor age, obesity, and a history of high alcohol intake have all been associated with fatty infiltration.

Donor selection remains highly subjective, and in the absence of reliable laboratory tests the decision whether to use a marginal graft is left to the judgment of the transplant surgeon. The definition of what constitutes a “marginal” or “extended” graft will continue to vary between centers until reliable parameters are available for prospectively predicting early graft function.17,24,25

Specific donor management may only begin after the diagnosis of brain death has been firmly established. Brain death is a catastrophic event associated with significant disturbances to many organ systems (Table 91-6).15Table 91-7 summarizes the key points of donor management (which are discussed in the following paragraphs) based on the current recommendations.3,17,27

Understanding and management of these changes is essential for optimal preservation of organs for transplantation.8,10,15 In general, there should be a shift in emphasis from more focused cerebral resuscitation, to optimization of oxygen delivery to other organs and tissues. This shift of management may only begin after consent has been obtained from the family. Routine care with frequent turning, protection of the eyes, frequent airway suctioning, physiotherapy to prevent atelectasis and pneumonia, gastric decompression, and limited exposure to prevent hypothermia are important aspects of this regimen. Intensive nursing care is needed, with a 1:1 or even 2:1 nurse:patient ratio.10

Successful transplantation of organs from donors is dependent on adequate resuscitation. Potential donors manifest profound hemodynamic and metabolic abnormalities, which can result in a loss of valuable organs. Autonomic instability and hypotension occur in approximately 80% of donors. Even with aggressive management as many as 25% of potential organ donors are lost due to hemodynamic instability. Even more organs are lost as a consequence of the high doses of vasopressors required to maintain adequate perfusion of the brain-dead organ donor.

Hypovolemia from osmotic agents given to treat high intracranial pressure, poorly treated diabetes insipidus, and traumatic blood loss all may contribute to hypotension. A sudden increase in intracranial pressure may cause hypotension and severe bradyarrhythmias because of parasympathetic stimulation from dural stretch, which is encountered after failure of the Cushing reflex, which causes severe systemic hypertension as a final effort to maintain cerebral perfusion in the face of drastically elevated intracranial pressure. As the vagal cardiomotor centers become ischemic, termination of parasympathetic activity occurs with resulting unopposed sympathetic stimulation. This marked increase in vascular resistance may lead to myocardial ischemia.10,13

Animal models have demonstrated profound systemic and pulmonary vasoconstriction with a massive systemic increase in catecholamine levels, termed the autonomic storm. This autonomic storm is followed by a transient shift of systemic intravascular fluid volume to the lungs. Cardiac output decreases and left atrial pressure may exceed pulmonary artery pressure. This may result in capillary wall disruption and leakage of protein-rich fluid into the pulmonary interstitium, resulting in pulmonary edema (also referred to as “neurogenic pulmonary edema”).10,13

A second major injury is the derangement of the hypothalamic-hypophyseal axis, with the associated changes in circulating plasma hormones. The loss of hypothalamic influence and sympathetic tone is characterized by a progressive decrease in serum norepinephrine and a decrease in systemic vascular resistance. This is analogous to a high cervical spinal cord transection. As a result, most potential organ donors require vasoactive agents to maintain blood pressure. The hypothalamic-pituitary axis dysfunction leads to neurogenic diabetes insipidus and a marked decrease in levels of thyroid hormone and cortisol in animal models. In the clinical setting the role these endocrine abnormalities play in the status of donors may vary among donors.4,8,10,13

Since the most crucial factor in determining optimal organ viability is the maintenance of adequate systemic perfusion pressure, invasive monitoring is recommended given the complex physiologic changes that are associated with brain death. This is particularly true if the heart and lungs are being considered for donation. Cautious repeated fluid challenges are administered until 10 cm H2O central venous pressure (CVP) is reached (assuming positive end-expiratory pressure [PEEP] = 5 cm H2O), thereafter aiming for the lowest CVP that maintains urine output and adequate perfusion pressure maintaining the CVP at 6 to 8 mm Hg. Crystalloid, colloid solutions, and blood products may be infused as indicated. Systolic blood pressure should not be allowed to fall below approximately 90 mm Hg. Red blood cells must be used to maintain a hemoglobin of at least 10 g/dL. Severe coagulopathy should be treated before organ procurement using appropriate blood component therapy. Low doses of dopamine or dobutamine at 2 to 10 μg/kg per minute are traditionally used, although arginine vasopressin at 0.5 to 4.0 U/h is an increasingly favored alternative. The systemic vascular resistance should be kept between 800 and 1200 dynes/s per cm2. If necessary, a combination of these drugs, each in the lower dosage range, often produce the best results, while maintaining at least 1 mL/kg per hour of urine output. Reduced diuresis despite adequate perfusion pressure can be increased by mannitol administration, at the dosage of 0.25 g/kg as an intravenous bolus. Fluid resuscitation therapy should be guided by data from a central venous catheter or a pulmonary artery catheter, with euvolemia (not hypervolemia) being the target of volume replacement therapy.

Dysrhythmias are quite common and should be treated aggressively. Persistent bradycardia is treated by isoproterenol infusion or even pacing. Minute ventilation should be adjusted to keep the CO2 and pH in a mild respiratory alkalosis. It is better to reduce the frequency of ventilation rather than tidal volume in order to prevent the development of atelectasis. PEEP is optimized and is regulated to maintain 95% oxygen saturation, and if possible the FiO2 should be no higher than 50%. Peak inspiratory pressures (PIP) are also important because high pressure results in barotrauma and impaired venous return to the heart, thereby compromising cardiac output. Pressure control modes of ventilation may be preferable for the minimization of these risks. Ideally PEEP is maintained at <7.5 and PIP at <30 cm H2O. Bronchoscopy may be necessary for pulmonary toilet, to collect samples for microbiology, and to reinflate atelectatic regions of the lung, thereby decreasing shunting. Bronchodilators should be administered. Continuous full monitoring is of course essential.

Maintenance of normal acid base balance in organ donors is often difficult. Partial pressure of arterial carbon dioxide (PCO2) should be maintained in the normal range and optimum pH is between 7.35 and 7.45. Glucose consumption is also decreased and parenteral or enteral nutrition must be decreased to around 50% to avoid hyperglycemia and unnecessary metabolic workload. Ongoing nutrition must be maintained, as it is associated with improved graft function, particularly for the liver graft. In the liver, glycogen stores are depleted within 12 hours of brain death, with suggested reduced resistance of the graft to ischemia. Persistent hyperglycemia despite reduced glucose administration can be treated with insulin. Loss of the hypothalamic-pituitary axis can result in diabetes insipidus. Associated electrolyte abnormalities are hypernatremia, hypocalcemia, hypokalemia, hypophosphatemia, and hypomagnesemia. In addition, the variety of strategies used to treat intracranial pressure may exaggerate the hypernatremic state. Aggressive correction of the electrolyte state should be performed and levels should be checked every 4 hours in order to prevent development of lethal dysrhythmias, myocardial dysfunction, and rhabdomyolysis. Sodium levels should be kept <155 mEq/dL, as liver primary graft nonfunction has been associated with hypernatremia. The diagnosis of central diabetes insipidus is easily made when more than 4 mL/kg per hour of dilute urine is produced while the serum sodium is above 145 mmol/L. Hypotonic fluids can be used to restore intravascular volume with a simple volume-for-volume replacement of the urine. Development of hyperglycemia may be caused by the dextrose or glucose in the hypotonic intravenous fluids; but on the other hand, it will help restore glycogen liver reserves in a setting of inadequate nutritional support. More practical is to use desmopressin (DDAVP) in a loading dose of 8 ng/kg, followed by an infusion of 4 ng/kg per hour and a reassessment and titration up or down every 30 minutes; alternatively, a 1-μg bolus every 2 hours can be used as long as the urine output remains >300 mL/h. DDAVP has a longer half-life and minimal vasopressor activity (2000:1) as compared to arginine vasopressin. Arginine vasopressin is particularly useful in hypotensive patients in a continuous infusion of aqueous vasopressin at the dosage of 0.5 U/hr, which can be titrated as necessary by monitoring the urine output. A relatively small percentage of organ donors are resistant to aqueous vasopressin. In these cases desmopressin acetate should be considered.

Warmed intravenous fluid, heated humidified oxygen, and warming blankets may need to be used to limit hypothermia. The core temperature should be maintained above 35°C. Hypothermia contributes to donor hemodynamic instability, myocardial depression, severe dysrhythmias, and coagulopathy, and may even cause cold diuresis and also predispose to sepsis. It is much better to prevent hypothermia, because once it has occurred it may be difficult to correct.

The recognition of the metabolic derangements following brain death, including autonomic storm and hypothalamic-pituitary axis dysfunction, has highlighted the need for hormonal resuscitation as an integral part of the donor management protocol.3–6,8,26–29. The recommended hormonal resuscitation consists of methylprednisolone in a 10–15 mg/kg bolus; triiodothyronine in a 4-μg bolus followed by a continuous infusion of 3 μg/h; arginine vasopressin in a 1-unit bolus, then a continuous infusion at 0.5 to 4 U/h, titrated to a systemic vascular resistance of 800 to 1200 dynes/s per cm2; and insulin 1 U/h titrated to maintain blood sugar at 120 to 180 mg/dL.6 The use of steroids is based on the intensive effort to increase the number of usable lungs given the low recovery rate of lungs from potential donors. Retrospective studies have repeatedly showed that high-dose steroid administration improved oxygenation in the brain-dead donor and was associated with increased rates of successful donation.30,31

Though initial evidence showed that vasopressin used with epinephrine maintains hemodynamic stability and tissue viability, its implementation was not adopted universally. Rather DDAVP was used, with the assumption that the effectiveness of arginine vasopressin was related to its treatment of the diabetes insipidus that is commonly found in organ donors. DDAVP is an analogue that is highly selective for the vasopressin V2-receptor subtype that is found in the renal collecting ducts, and has no vasopressor activity in humans, which is mediated by V1-receptors on vascular smooth muscle. Arginine vasopressin was in fact abandoned due to concerns that the vasoconstrictive effect could be harmful for donor organs. This resulted in unnecessarily excessive fluid resuscitation with crystalloid, colloid, and blood products, along with higher doses of vasopressor agents with widely recognized adverse effects. Many transplant centers consider a donor heart to be unsuitable if dopamine requirements exceed 10 to 15 μg/kg per minute, because at such doses it can also affect both kidney and liver.27

Hemodynamic instability has also been suggested to be a consequence of diminished levels of circulating thyroxin, leading to reduced myocardial energy stores and a shift from aerobic to anaerobic metabolism, with the subsequent accumulation of lactate. These observations were initially described in animal studies, and the administration of thyroid hormone replacement to human brain-dead donors has shown improvement in the cardiovascular status of donors, with reduction in the inotropic support, particularly in hemodynamically unstable organ donors. This benefit is most pronounced in cardiac transplantation and heart graft function.26

Considerable debate is ongoing regarding the role of thyroid hormone therapy in the management of organ donors. Several studies have shown no correlation between thyroid hormone levels and hemodynamic status. Some observed no beneficial effect and a trend toward worsening metabolic acidosis following thyroid hormone administration. Contrarily, the implementation of the three-hormone resuscitation therapy, with methylprednisolone, arginine vasopressin, and triiodothyronine or levothyroxin, has been associated with an increased number of transplanted hearts and improved short-term graft function.26,27 The selection of donors who are predicted to benefit from hormonal resuscitation has been outlined. After conventional management to adjust volume status, anemia, and metabolic abnormalities, the recommendation is that an echocardiogram be obtained to rule out structural abnormalities and document the ejection fraction. If the ejection fraction is <45%, a pulmonary artery catheter is placed and hormonal resuscitation is instituted. Subsequent cardiac function can be monitored using the pulmonary artery catheter.